This invention relates to specific molecular weight fractions of hyaluronic acid (hereinafter referred to as "HA") which have therapeutic applications and which are non-inflammatory when utilized. One of the HA fractions of this invention is useful for facilitating wound healing, while the second HA fraction is useful for intraocular use to substitute for endobulbar fluids or for intraarticular injection for use in treating damaged bone joints.
Hyaluronic acid is a naturally occurring heteropolysaccharide consisting of alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine. HA is a linear polymer of high molecular weight, generally up to about 8 to 13 million, and has been found in cell coats, the extracellular ground substance of connective tissues of vertebrates, in the synovial fluid in joints, in the endobulbar fluids of the eye, in human umbilical cord tissue, and in rooster combs.
Previous investigations on the use of HA are included in the work of Balazs, U.S. Pat. No. 4,141,973, directed to a fraction of HA useful for replacing endobulbar fluids, as well as other therapeutic applications. This patent, however, is specifically directed to an HA fraction having an average molecular weight greater than about 750,000, and preferably greater than about 1,200,000. Balazs specifically teaches that fractions of HA having an average molecular weight of less than 750,000 are not therapeutically useful because of their inflammatory activity. These lower molecular weight fractions of HA are discarded by Balazs. However, this results in discarding about 90% of the total amount of available HA obtainable from the source tissues, resulting in a use of only a small amount (about 10%) of the available HA.
Contrary to the teachings of Balazs, the present inventors have discovered that lower molecular weight fractions of HA do indeed have useful pharmaceutical activity. Thus, according to the present invention, about 80% of the HA obtainable from various sources is utilized. In particular, the present inventors have discovered one fraction of HA which is useful for stimulating wound healing, and a second fraction of HA which is useful for intraocular injections to substitute for the endobulbar liquids in the eye and for intraarticular injections as a treatment for damaged joints.